The present invention relates to the use of specific ceramides as skin-depigmenting agent, and also to a process for depigmenting the skin.
Human skin colour depends on various factors, and in particular on the seasons of the year, on race and on gender; it is mainly determined by the nature and the concentration of melanin produced by melanocytes. Melanocytes are specialized cells which synthesize melanin by means of specific organelles, melanosomes. In addition, at various times in their life, certain individuals experience the appearance of dark and/or coloured spots on the skin and more especially on the hands, which give the skin a heterogeneity. These spots are also due to a high concentration of melanin in the keratinocytes located at the skin surface.
The use of harmless topical depigmenting substances that are very effective is most particularly desired with a view to treating regional hyperpigmentations due to melanocyte hyperactivity, such as idiopathic melasmas, occurring during pregnancy (“pregnancy mask” or chloasma) or oestro-progestatin contraception, localized hyperpigmentations due to benign melanocyte hyperactivity and proliferation, such as senile pigmentation spots referred to actinic lentigo, accidental hyperpigmentations, possibly due to post-lesional cicatrization or photosensitization, and also certain forms of leukoderma, such as vitiligo. For the latter (the cicatrizations possibly resulting in a scar that gives the skin a whiter appearance), since it is not possible to repigment the lesioned skin, the process is finished off by depigmenting the areas of residual normal skin so as to give the skin as a whole a homogeneous white tint.
The mechanism of formation of skin pigmentation, i.e. of the formation of melanin, is particularly complex and involves, schematically, the following main steps:
Tyrosine→Dopa→Dopaquinone→Dopachrome→Melanin
Tyrosinase (monophenol dihydroxyl phenylalanine:oxygen oxidoreductase EC 1.14.18.1) is the essential enzyme involved in this series of reactions. It catalyses in particular the reaction for conversion of tyrosine to Dopa (dihydroxyphenylalanine) by virtue of its hydroxylase activity and the reaction for conversion of Dopa to dopaquinone by virtue of its oxidase activity. This tyrosinase acts only when it is in the maturation state under the action of certain biological factors.
A substance is recognized being a depigmenting substance if it acts directly on the vitality of epidermal melanocytes where melanogenesis takes place, and/or if it interferes with one of the steps of melanin biosynthesis, either by inhibiting one of the enzymes involved in melanogenesis, or by intercalating as a structural analogue of one of the chemical compounds of the melanin synthesis chain, which chain can then be blocked, and thus ensuring depigmentation.
The substances most commonly used as depigmenting agents are, more particularly, hydroquinone and its derivatives, in particular its ethers such as hydroquinone monomethyl ether and hydroquinone monoethyl ether. Although they have a certain level of effectiveness, these compounds are, unfortunately, not free of side effects on account of the toxicity that they entail, which may make them complicated, or even dangerous, to use. This toxicity arises from the fact that they intervene in fundamental mechanisms of melanogenesis by killing cells which then run the risk of disturbing their biological environment and which consequently oblige the skin to eliminate them by producing toxins.
Thus, hydroquinone is a compound which is particularly irritant and cytotoxic to melanocytes, and whose total or partial replacement has been envisaged by many authors.
Substances have thus been sought which do not intervene in the mechanism of melanogenesis but which act upstream on tyrosinase by preventing its activation and are, as a result, much less toxic. Kojic acid is commonly used as an inhibitor of tyrosinase activation, said kojic acid complexing the copper present in the active site of this enzyme. Unfortunately, this compound is unstable in solution, thereby somewhat complicating the manufacture of the composition.
There remains the need for a new agent for whitening human skin which has an action that is as effective as the known agents, but which does not have their drawbacks, i.e. which is nonirritant, nontoxic and/or nonallergenic for the skin.